Analysis of brain adrenergic receptors in dopamine-beta-hydroxylase knockout mice

Brain Res. 2006 Sep 13;1109(1):45-53. doi: 10.1016/j.brainres.2006.06.033. Epub 2006 Jul 18.


The biosynthesis of norepinephrine occurs through a multi-enzymatic pathway that includes the enzyme dopamine-beta-hydroxylase (DBH). Mice with a homozygous deletion of DBH (Dbh-/-) have a selective and complete absence of norepinephrine. The purpose of this study was to assess the expression of alpha-1, alpha-2 and beta adrenergic receptors (alpha1-AR, alpha2-AR and beta-AR) in the postnatal absence of norepinephrine by comparing noradrenergic receptors in Dbh-/- mice with those in Dbh heterozygotes (Dbh+/-), which have normal levels of norepinephrine throughout life. The densities of alpha1-AR, alpha2-AR and beta-AR were assayed with [3H]prazosin, [3H]RX21002 and [125I]-iodo-pindolol autoradiography, respectively. The alpha2-AR agonist high affinity state was examined with [125I]-para-iodoclonidine autoradiography and alpha2-AR functionality by alpha2-AR agonist-stimulated [35S]GTPgammaS autoradiography. The density of alpha1-AR in Dbh-/- mice was similar to Dbh+/- mice in most brain regions, with an up-regulation in the hippocampus. Modest decreases in alpha2-AR were found in septum, hippocampus and amygdala, but these were not reflected in alpha2-AR functionality. The density of beta-AR was up-regulated to varying degrees in many brain regions of Dbh-/- mice compared to the heterozygotes. These findings indicate that regulation of noradrenergic receptors by endogenous norepinephrine depends on receptor type and neuroanatomical region.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Autoradiography / methods
  • Brain / drug effects
  • Brain / growth & development
  • Brain / metabolism*
  • Dopamine beta-Hydroxylase / deficiency*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Idazoxan / analogs & derivatives
  • Idazoxan / metabolism
  • Isotopes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pindolol / metabolism
  • Prazosin / metabolism
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Receptors, Adrenergic, alpha-2 / genetics
  • Receptors, Adrenergic, alpha-2 / metabolism*


  • Isotopes
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Pindolol
  • 2-methoxyidazoxan
  • Dopamine beta-Hydroxylase
  • Prazosin
  • Idazoxan